PANoptosis in vascular smooth muscle cells regulated by TNF-α/IL-1ß can be a new target for alleviating the progression of abdominal aortic aneurysm.

PANoptosis is an inflammatory programmed cell death (PCD) regulated by multifaceted PANoptosome complexes with major features of pyroptosis, apoptosis, and/or necroptosis that cannot be accounted for by any of these PCD pathways alone. The aim of this study was to investigate the role of PANoptosis on the occurrence and development of abdominal aortic aneurysm (AAA). Clinical samples of patients with AAA, angiotensin II (ANG II)-induced AAA mouse model, and ANG II-induced vascular smooth muscle cells (VSMCs) in vitro model were used for investigation on PANoptosis features. The expressions of ZBP1, AIM2, and other markers related to pyroptosis, apoptosis, and necroptosis elevated obviously in aortic wall tissues of patients with AAA, mice with AAA, and ANG II-treated VSMCs. ANG II treatment increased inflammatory cytokines levels in VSMCs. The stimulation of tumor necrosis factor-α (TNF-α) or interleukin-1ß (IL-1ß) alone promoted VSMCs death, and the effect of TNF-α combined with IL-1ß is more obvious. The expressions of ZBP1, AIM2, and related markers of pyroptosis, apoptosis, and necroptosis were increased by TNF-α and IL-1ß combined treatment. Inhibition of TNF-α and/or IL-1ß in mice with AAA improved the AAA pathology, reduced the loss of VSMCs, decreased the expression of ZBP1 and AIM2, and markers associated with pyroptosis, apoptosis, and necroptosis. PANoptosis features were observed in aortic wall tissues of patients with AAA, mice with AAA, and ANG II-treated VSMCs. The inhibition of TNF-α and IL-1ß can alleviate PANoptosis in mice with AAA, which provides a new strategy for the prevention and treatment of AAA.NEW & NOTEWORTHY Early detection, diagnosis, and treatment are very important to improve the quality of life and prognosis of patients with abdominal aortic aneurysm (AAA). Based on the findings of apoptosis, necroptosis, and pyroptosis (PANoptosis) in AAA clinical samples, this study further explored the molecular mechanism in vivo and in vitro. Specifically, inhibition of tumor necrosis factor-α and interleukin-1ß can reduce PANoptosis in vascular smooth muscle cell and thus alleviate the process of AAA.

Inhibition of XIST attenuates abdominal aortic aneurysm in mice by regulating apoptosis of vascular smooth muscle cells through miR-762/MAP2K4 axis.

Abdominal aortic aneurysm (AAA) is a common chronic aortic degenerative disease. Long non-coding RNA X-inactive specific transcript (XIST) is associated with the progression of AAA, while the underlying mechanism is still unclear. We investigated the functional role of XIST in AAA. AAA mouse model was established by administration of Angiotensin II (Ang II). Primary mouse vascular smooth muscle cells (VSMCs) were separated from the abdominal aorta of Ang II-induced AAA mice, and then treated with Ang II. XIST was highly expressed in Ang II-treated VSMCs. Cell proliferation ability was decreased and apoptosis was increased in VSMCs following Ang II treatment. XIST knockdown reversed the impact of Ang II on cell proliferation and apoptosis in VSMCs. XIST promoted mitogen-activated protein kinase kinase 4 (MAP2K4) expression by sponging miR-762. XIST overexpression suppressed cell proliferation and apoptosis of Ang II-treated VSMCs by regulating miR-762/MAP2K4 axis. Finally, Ang II-induced AAA mouse model was established to verify the function of XIST in AAA. Inhibition of XIST significantly attenuated the pathological changes of abdominal aorta tissues in Ang II-induced mice. The expression of miR-762 was inhibited, and MAP2K4 expression was enhanced by XIST knockdown in the abdominal aorta tissues of AAA mice. In conclusion, these data demonstrate that inhibition of XIST attenuates AAA in mice, which attributes to inhibit apoptosis of VSMCs by regulating miR-762/MAP2K4 axis. Thus, this study highlights a novel ceRNA circuitry involving key regulators in the pathogenesis of AAA.

LncRNA GAS5 promotes abdominal aortic aneurysm formation through regulating the miR-185-5p/ADCY7 axis.

One of the causes of abdominal aortic aneurysm (AAA) is the apoptosis of vascular smooth muscle cells. Many long noncoding RNA (lncRNAs) have been implicated in AAA formation. However, the mechanism of growth arrest-specific 5 (GAS5) in AAA formation is not yet clear. The expression levels of GAS5, microRNA-185-5p (miR-185-5p) and adenylate cyclase 7 (ADCY7) were determined by quantitative real-time PCR. Angiotensin II (ANGII) was used to induce AAA cell models. Cell viability was detected by MTT assay, and cell apoptosis was assessed by flow cytometry. Western blot analysis was used to test the protein expression levels. Besides, a dual-luciferase reporter assay was used to identify the mechanism of GAS5. GAS5 was upregulated in AAA tissues and ANGII-induced human aortic smooth muscle cells (HASMCs). GAS5 overexpression inhibited proliferation and promoted apoptosis and inflammatory response in ANGII-induced HASMCs, while its knockdown had the opposite effects. MiR-185-5p could be absorbed by GAS5, and its inhibitor could invert the effects of GAS5 silencing on proliferation, apoptosis and inflammatory response in ANGII-induced HASMCs. ADCY7 was a target of miR-185-5p. ADCY7 knockdown increased proliferation, while decreased apoptosis and inflammatory response in ANGII-induced HASMCs. Also, overexpressed ADCY7 reversed the effect of miR-185-5p overexpression on proliferation, apoptosis and inflammatory response in ANGII-induced HASMCs. GAS5 positively regulated the ADCY7 expression to inhibit the activity of the AKT signaling pathway by sponging miR-185-5p. LncRNA GAS5 contributed to AAA formation through regulating HASMCs proliferation, apoptosis and inflammatory response, which might provide new ideas for the treatment of AAA.

Complete Endovascular Reconstruction of the Canine Ascending Aorta, Aortic Arch, and Supra-Aortic Vessels by Implanting a New Unibody Outer Double-Branched Stent-Graft.

PURPOSE: We evaluated the feasibility and safety of using a new unibody outer double-branched stent-graft system to reconstruct the canine ascending aorta, aortic arch, and supra-aortic vessels. MATERIALS AND METHODS: The outer-branched stent-graft was a unibody design. The branched stent-graft consisted of a main stent-graft and 2 branches. The introducer system included a tri-channel catheter, 2 detachable sleeves, a front fixing device, a constraining wire, and a curved outer sheath. The branched stent-graft was loaded into the introducer system. Ten adult mongrel dogs underwent general anesthesia, and the branched stent-grafts were deployed into the canine ascending aorta, aortic arch, and supra-aortic vessels by the introducer system. All animals were followed up for 3 months. At the end of the follow-up period, computed tomographic angiography (CTA) was performed to observe the patency of the branched stent-grafts. RESULTS: The mean operation time was 142.7±13.7 minutes. The mean fluoroscopy time was 20.73±2.22 minutes. The mean dosage of contrast agent was 95.9±8.7 mL. During the operation, the tri-channel catheters successfully paralleled the wires in the aorta. All 10 branched stent-grafts were successfully implanted into the canine ascending aorta and aortic arch. There were no symptoms of cerebral embolization and no incision infection during the follow-up period. Computed tomographic angiography and specimens showed that the branched stent-grafts and native vessels were patent, the inner surfaces of the branched stent-grafts were covered by neointima, and there was no retrograde aortic dissection in the ascending aorta. CONCLUSIONS: This animal research demonstrated that the unibody outer double-branched stent-graft system could be applied to reconstruct the canine ascending aorta, aortic arch, and supra-aortic vessels. CLINICAL IMPACT: Thoracic endovascular aortic repair has been the main treatment method for aortic aneurysms or dissections involving the descending thoracic aorta. However, the aortic arch and ascending aorta remain the last segments of the aorta without a validated and routinely used endovascular option. In this research, we designed a new unibody outer branched stent-graft system to reconstruct the distal ascending aorta, aortic arch and supra-aortic vessels. The unibody outer branched stent-graft system could be applied to treat aortic pathologies which involve the middle and distal proximal ascending aorta, aortic arch and proximal descending aorta.

Clinical characteristics and long-term outcomes of endovascular treatment of renal artery fibromuscular dysplasia with branch lesions.

BACKGROUND: Renal artery fibromuscular dysplasia (FMD) can cause arterial stenosis, dissection, and aneurysm of renal arteries. This study aimed to analyze the clinical characteristics and evaluate the long-term outcomes of renal branch artery FMD in children and adults. METHODS: Sixty-one patients with renal artery FMD underwent endovascular treatment, including 23 children and 38 adults. They were divided into two groups, the main artery FMD group (n = 40, with severe stenosis located in the main renal artery) and the branch artery FMD group (n = 21, with only the branch lesions in unilateral or bilateral branch artery). The clinical characteristics and long-term outcomes of these pediatric and adult patients were evaluated. RESULTS: The incidence of branch FMD was higher in children than in adults (P = 0.005). Thirteen children showed one or more branch artery involvements. Hypertension and headache were the most common symptoms. The branch aneurysm with coexisting stenosis was more common in patients with branch artery FMD. During the follow-up, blood pressure was normal in 8 patients and lowered in 11 patients in the branch FMD group. The patient's glomerular filtration was increased in 61 patients (P < 0.001). Four-year freedom from reintervention in 21 branch artery FMD patients was lower than that in 40 main artery FMD patients (P < 0.05). CONCLUSIONS: A higher incidence of renal branch artery FMD was observed in children than in adults. Endovascular treatment with balloon angioplasty can be used for treating renal branch artery FMD.

Primary results of abdominal aortic aneurysm screening in the at-risk residents in middle China.

BACKGROUND: There is a lack of information on the epidemiological data and risk factors associated with abdominal aortic aneurysm (AAA) in Chinese population. We reported the primary results from screening five-community population in Middle China for AAA. METHODS: From March 2014 to October 2015, an AAA screening program was performed in three urban and two rural communities. These communities were randomly selected. All at-risk residents (a total of 6925) aged 40 years or older were invited to attend an ultrasound scan for AAA. At-risk population was defined as having a family history of first-degree relative diagnosed with AAA; or smoking and aged 55 years or older; or having a history of CAD, cerebrovascular disease, hypercholesterolemia, obesity (BMI ≧ 26 kg/m2) or hypertension. RESULTS: The study investigated 5402 subjects and the mean age of them was 61.2 ± 10.4 years old. It included 2847 women aged 62.5 ± 10.4 years and 2555 men aged 59.7 ± 10.2 years. The mean maximum infrarenal aortic diameter (Max-IAD) was 15.0 ± 2.7 mm (from 4.1 to 51.5 mm). Eighteen people (aged 68.0 ± 10.4 years) with AAAs were detected (prevalence rate was 0.33%), and the prevalence rate in males was higher than in females (0.55% vs 0.14%, respectively, P = 0.009). Additionally, the screened subjects aged 55 to 75 years had a higher prevalence rate of AAA than other age groups (0.51% vs 0.11%, respectively, P = 0.016). CONCLUSION: The mean Max-IAD of the screened population in Middle China was apparently small by comparison with other reports. The result of low prevalence rate of AAA didn't support routine screening in Chinese population. The at-risk males aged 55 to 75 years should be targeted for further screening.

Effect of Atorvastatin on lower extremity function of patients with hypertension and peripheral arterial disease.

This paper aims to discuss the short-term effect of Atorvastatin on lower-extremity function of patients with hypertension and peripheral arterial disease (PAD). 40 patients with hypertension and ankle-brachial index (ABI) less than 0.9 were divided into the control group (20 cases) and Atorvastatin group (20 cases) and treated for 6 months. The variation between the 6-min walk and the gait speed of 4-m-walk before and after the treatment were respectively observed. With regard to the two groups, differences of the drop-out values before and after the treatment were adjusted in accordance with gender, ages, body mass index (BMI), difference values of systolic pressure, ABI, difference values of total cholesterol (TC), difference values of low density lipoprotein, triacylglycerol, smoking and drug-taking situation. After the treatment, the 6-min walk had no obvious change between the two groups (P>0.05), but the 4-m normal and rapid walking speed changed obviously (P<0.01). Short-term therapy with atorvastatin can significantly delay the decline of the walking speed in short distance and improve the lower-extremity function of patients with hypertension and PAD.

Mechanism and Management of Retrograde Type A Aortic Dissection Complicating TEVAR for Type B Aortic Dissection.

BACKGROUND: This study is to investigate the causes, treatment methods, and preventive measures of retrograde type A aortic dissection (RAAD) complicating thoracic endovascular aortic repair (TEVAR) for type B aortic dissection (TBAD). METHODS: From January 2005 to December 2013, 360 TBAD patients receiving TEVAR were enrolled in this study. Among them, 304 cases were male and 56 cases were female. They were from 19 to 85 years old, with a mean age of 52 ± 12.8 years old. The average follow-up time was 32 ± 11.3 months (3-63 months), the follow-up rate was 69.1% (249 cases), and the lost rate was 30.9% (111 cases). The reasons and the treatment methods of RAAD complicating TEVAR for TBAD were analyzed. RESULTS: There were 5 cases of RAAD complicating TEVAR in TBAD (1.4%) patients, among them, 4 cases were male and 1 case was female. TEVAR operation failed in 1 case because of RAAD occurrence during TEVAR. This case was treated with open operation. In the other 4 cases, TEVAR operation was successfully carried out. During follow-up, RAAD was found in 3 cases within 1 month after TEVAR and in 1 case at 1 year after TEVAR. Conservative treatment was applied to 2 cases, whereas surgical operation treatment was performed in the other 3 cases. One case of conservative treatment patient was dead, and the other 4 cases are still alive. CONCLUSIONS: Incomplete design of stent-graft system, rough handling and presence of vascular wall lesions are the main reasons of RAAD complicating TEVAR for TBAD. Surgical operation is the most effective treatment measure for RAAD complicating TEVAR for TBAD.

Study on the small intestine absorptive kinetics characters of tanshinol and protocatechualdehyde of Salvia miltiorrhiza extracts in rats in vivo.

In order to provide scientific basis for clinical selection of drugs, to compare and analyze the effective constitutes and the intestinal absorption in vivo in rats of the compound salvia tablets and compound salvia dropping pills (taken as the representatives). Determine the contents of tanshinol, protocatechuic aldehyde, salvianolic acid B and tanshinone II A, cryptotanshinone, ginseng saponin Rg1 and Rb1 in the compound salvia tablets and compound salvia dropping pills by High Performance Liquid Chromatography (HPLC). The intestinal absorption condition of the tanshinol, protocatechuic aldehyde, salvianolic acid B of the compound salvia tablets and compound salvia dropping pills in rats were detected by intestinal perfusion experiment. Only the intake of protocatechuic aldehyde in the compound salvia tablets was higher than in the compound dropping pills, the intake of the other 6 effective constitutes were all lower than in the compound dropping pills. The intestinal absorption of protocatechuic aldehyde was rather complete, while the intestinal absorption of tanshinol and salvianolic acid B were not significant. The duodenum was the main absorption region of these three components. The absorption of protocatechuic aldehyde was different in different regions of the intestines. Each intake of the effective constitutes in the tablets and dropping pills were significantly different, and the rat intestinal absorption of part of the components were different.

Ultrasensitive colorimetric carcinoembryonic antigen biosensor based on hyperbranched rolling circle amplification.

In this study, a hyperbranched rolling circle amplification (HRCA)-based colorimetric biosensor for carcinoembryonic antigen (CEA) is developed with high sensitivity and specificity. A CEA aptamer can bind with its target (CEA) to form a complex due to their high affinity, and the introduced CDNA cannot hybridize with the aptamer. Thus, free CDNA can propagate the HRCA reaction to form a large number of single-stranded DNA (ss-DNA). ss-DNA can be easily adsorbed onto AuNPs and prevent salt-induced AuNPs aggregation, which causes the change in the color of the system. It is found that the absorbance intensity ratio (A520/A660) has a linear relationship with the concentration of the target in the range of 5 pM-0.5 nM, and the detection limit is as low as 2 pM (S/N = 3).

METTL3-METTL14 complex induces necroptosis and inflammation of vascular smooth muscle cells via promoting N6 methyladenosine mRNA methylation of receptor-interacting protein 3 in abdominal aortic aneurysms.

Abdominal aortic aneurysms (AAA) have the highest incidence and rupture rate of all aortic aneurysms. The N6 methyladenosine (m6A) modification is closely associated with angiotensin (Ang II)-induced aortic diseases. This study aimed to identify whether the m6A writer METTL3/METTL4 regulates rip3 mRNA expression in AAA. To induce the mouse AAA model, apolipoprotein E-deficient (ApoE-/-) mice were subcutaneously infused with Ang II, and C57BL/6 mice were infused with type I elastase. Vascular smooth muscle cells (VSMCs) were induced with Ang II. Necroptosis was detected using an Annexin V-FITC/PI apoptosis detection kit, and ELISA assays measured inflammatory cytokines. The RNA immunoprecipitation-qPCR determined the methylated rip3 mRNA level. The increased expressions of inflammatory factors, aortic adventitia injury, degradation of elastin, and CD68-positive cells suggested the successful establishment of mouse AAA models. In AAA aorta wall tissues, the m6A modification level and the expression of METTL3/METTL14 were elevated. In Ang II-induced VSMCs, necroptosis and inflammatory cytokines in the supernatants were increased. RNA immunoprecipitation and co-immunoprecipitation assays confirmed the binding between the METTL3-METTL14 complex and rip3 mRNA, the interaction between YTHDF3 and rip3 mRNA, and between the METTL3-METTL14 complex and SMAD2/3. Interference with METTL3/METTL14 attenuated VSMC necroptosis, inflammatory response, and the AAA pathological process in vivo. The METTL3-METTL14 complex, which was increased by the activation of the SMAD2/3, elevated the m6A modification of rip3 mRNA by promoting the binding between YTHDF3 and rip3 mRNA, thus contributing to the progression of AAA. The activation of SMAD2/3 in VSMCs of abdominal aortic wall tissues is stimulated by Ang II. Subsequently, it promotes METTL3 METTL14 complex mediated m6A modification of rip3 mRNA. Meanwhile, the level of rip3 mRNA becomes more stable under the m6A reader of YTHDF3, which increases the protein level of RIP3 and further induces VSMC necroptosis. In addition, cell debris induces inflammatory factors in neighboring VSMCs and recruit monocytes/macrophages to the lesion.

Retrograde type A aortic dissection during or after thoracic endovascular aortic repair: a single center 16-year experience.

Objective: This article aims to investigate the incidence rate of retrograde type A aortic dissection (RTAD) and the risk factors of RTAD in relation to thoracic endovascular aortic repair (TEVAR). Methods: Patients with thoracic aortic disease who underwent TEVAR at Henan Provincial People's Hospital from January 2004 to December 2019 were enrolled in the present research. The risk factors associated with RTAD following TEVAR using univariate and multiple logistic regression analyses. Results: During the study period, A total of 1,688 TEVAR patients were included in this study, and of these, 1,592 cases were included in the type B aortic dissection (TBAD) group, and 96 cases were included in the non-TBAD group. There were 1,230 cases of aortic dissection and 362 cases of aortic intramural hematoma and/or penetrating ulcer in the TBAD group. The non-TBAD group included 68 cases of thoracic aortic aneurysm, 21 cases of thoracic aortic pseudoaneurysm, and seven cases of congenital aortic coarctation. The overall incidence rate of RTAD was 1.1% (18/1,688) in patients, all of which occurred in the TBAD group. The cohort comprised 18 RTAD patients with an average age of 56.78, consisting of 13 males and 5 females. Among them, 13 individuals exhibited hypertension. Ten instances happened within the TEVAR perioperative period, including two cases during the surgery, six cases occurred within three months, two cases occurred after one year, and the longest interval was 72 months following TEVAR. TEVAR was successfully implemented in 17 patients, while the operation technique was temporarily altered in one case. The new entry position for RTAD was identified as the proximal region of the stent graft (SG) in 13 patients, while in five cases, the entry site was more than 2 cm away from the proximal region of the SG. 17 cases were at the greater curvature of the aorta, and one case was at the lesser curvature. Multivariate logistic regression analysis revealed that the SG oversizing ratio is a relevant risk factor for RTAD. However, ascending aortic diameter, aortic arch type, SG type, and anchored region were not directly related to the occurrence of RTAD. Conclusion: RTAD is a rare yet catastrophic complication. It could occur both during the procedure, early and late postoperative periods. Maintaining an appropriate SG oversizing ratio is crucial to minimize the risk of RTAD.

Application of transmesenteric vein extrahepatic portosystemic shunt in treatment of symptomatic portal hypertension with cavernous transformation of portal vein.

Purpose: To evaluate the feasibility and efficacy of a transmesenteric vein extrahepatic portosystemic shunt (TmEPS) for the treatment of cavernous transformation of the portal vein (CTPV). Materials and methods: The clinical data of 20 patients with CTPV who underwent TmEPS between December 2020 and January 2022 â€‹at Henan Provincial People's Hospital were retrospectively collected. The superior mesenteric vein (SMV) trunk was patent or partially occluded in these patients. An extrahepatic portosystemic shunt between the inferior vena cava and the SMV was established using a stent graft through an infraumbilical median longitudinal mini-laparotomy. The technical success, efficacy, and complication rates were evaluated, and the pre- and postoperative SMV pressures were compared. Patients' clinical outcomes and shunt patency were assessed. Results: TmEPS was successfully performed in 20 patients. The initial puncture success rate of the balloon-assisted puncture technique is 95%. The mean SMV pressure decreased from 29.1 â€‹± â€‹2.9 â€‹mmHg to 15.6 â€‹± â€‹3.3 â€‹mmHg (p â€‹< â€‹0.001). All symptoms of portal hypertension resolved. No fatal procedural complications occurred. During the follow-up period, hepatic encephalopathy occurred in two patients. The remaining patients remained asymptomatic. All shunts were patent. Conclusions: TmEPS is a feasible, safe, and effective treatment option for patients with CTPV.

Long Noncoding RNA DSCAM-AS1 Facilitates Proliferation and Migration of Hemangioma Endothelial Cells by Targeting miR-411-5p/TPD52 Axis.

Background: Diagnosed as a kind of vascular neoplasm of infancy, hemangioma (HA) occurs mainly due to the aberrant proliferation of endothelial cells. Existing evidence has manifested the close relationship of long noncoding RNAs (lncRNAs) with the pathogenesis of HA. Although lncRNA DSCAM antisense RNA 1 (DSCAM-AS1) has been revealed to be implicated in the progression of human diseases, the underlying mechanism DSCAM-AS1 exerts in HA formation is unclear. Aims: To figure out how DSCAM-AS1 may regulate the progression of human hemangioma endothelial cells (HemECs). Methods: DSCAM-AS1 expression was verified through RT-qPCR detection. Functional assays including EdU assay, colony formation assay, flow cytometry analysis, TUNEL assay, and transwell assay were applied to evaluate cell proliferation, apoptosis, and migration upon DSCAM-AS1 knockdown. Moreover, RNA pull-down assay, luciferase reporter assay, RIP assay, and other mechanism experiments were utilized for evaluating the correlation of DSCAM-AS1 and RNAs in HemECs. Results: DSCAM-AS1 knockdown inhibited proliferative capability and migratory capability of HemECs whereas expedited apoptosis. Molecular mechanism results testified DSCAM-AS1 could function as a ceRNA to bind miR-411-5p in HemECs. Besides, it was confirmed that tumor protein D52 (TPD52) served as a downstream target of miR-411-5p in HemECs. More importantly, related rescue assays uncovered that elevated expression of TPD52 or inhibited expression of miR-411-5p reversed the repressive progression of HemECs mediated by DSCAM-AS1 depletion. Conclusion: DSCAM-AS1 expedited HA progression via miR-411-5p/TPD52 pathway, which provided a novel therapeutic option for HA treatment.

A canine model of aortic arch aneurysm created with autologous pericardium.

Background: To establish a canine model of aortic arch aneurysm that is suitable for research on new devices and techniques applied to the aortic arch. Materials and methods: Fifteen mongrel dogs underwent surgery. The autologous pericardial patch was sewn on the aortotomy site in the anterior wall of the aortic arch. The animals were followed up for 3 months postoperatively. Computed tomography angiography was used to visualize and measure the aneurysm model. Hematoxylin and eosin staining was used to observe the histological characteristics of the aneurysm model. Changes in aneurysm diameter over time were analyzed using analysis of variance. Results: One dog died of hemorrhage during surgery. Fourteen dogs survived the surgical procedure. Two of them died on the first postoperative day because of ruptures at the suturing margin. The diameter of the aneurysm model was twice as large as that of the aortic arch. There was no significant change in the maximum diameter of the aneurysm model during the follow-up period. Conclusions: We established a controllable and stable aortic arch aneurysm model created with an autologous pericardium patch. The aneurysm model can be used to research endoleaks after thoracic endovascular aortic repair and new endovascular techniques can be applied to the aortic arch.

Clinical Results and Aortic Remodeling After Endovascular Treatment for Complicated Type B Aortic Dissection With the "Fabulous" Stent System.

OBJECTIVE: To report the clinical outcomes and aortic remodeling after the implantation of a self-developed, biomechanically optimized, two-stage thoracic stent system named Fabulous. BACKGROUND: Given the efficacy of the PETTICOAT concept, the benefits of Fabulous and the behavior of remodeling in different segments need further investigation. METHODS: This is a prospective and multicenter study. From 2017 to 2019, 145 patients (mean age, 56.6 years; 88.3% male) from 14 centers were included in this cohort. The clinical results and core laboratory results were from a central electronic data capture system. Computed tomographic angiography was performed preoperatively, 1 month, 6 months and yearly thereafter and was used for volumetric analysis by 3mensio (Bilthoven, The Netherlands). After the 1-year follow-up, 97.2 and 87.6% of the clinical and imaging results of the eligible patients were available. RESULTS: Both stent grafts and bare stents were successfully delivered in place in 100% of the patients. The 30-day mortality and 1-year freedom from all-cause mortality were 2.1 and 96.6%, respectively. The incidence of entry flow was 11.7% at 30 days and 6.2% at 365 days. No cases of stent-induced new entry (SINE) or reintervention were observed. After the 1-year follow-up, the true lumen/overall volume ratio reached 88%. The following subdivided segment volume changes were recorded: stent graft segment TL +56%; FL -92%, bare stent segment TL +32%; FL -75%, and there were no significant changes in the visceral segment. CONCLUSIONS: These outcomes indicated that there were favorable clinical benefits of Fabulous stent system. This device achieved a low short-term mortality and a low incidence of reintervention. In addition, patients undergoing Fabulous stent system implantation showed remodeling both on descending aorta and on the distal aorta. The volume changes in the TL and FL varied in the different segments. The long-term follow-up is still ongoing.

M1 macrophages-derived extracellular vesicles elevate microRNA-185-3p to aggravate the development of atherosclerosis in ApoE-/- mice by inhibiting small mothers against decapentaplegic 7.

OBJECTIVE: Extracellular vesicles (EVs) are vital mediators of transferring microRNAs (miRNAs). We focused on effect of miR-185-3p that mediated by macrophages-derived EVs on atherosclerosis (AS) by targeting small mothers against decapentaplegic 7 (Smad7). METHODS: EVs were extracted from M1 macrophages and identified. ApoE-/- mice were treated with EVs, EVs containing miR-185-3p inhibitor or mimic, then the pathological changes of mouse aorta were observed. The levels of blood lipid, cell adhesion molecules, oxidative stress factors, inflammatory factors, and proliferation and apoptosis of vascular endothelial cells were assessed. Expression of miR-185-3p and Smad7 was detected and the targeting relationship between miR-185-3p and Smad7 was validated. RESULTS: MiR-185-3p was upregulated while Smad7 was downregulated in atherosclerotic mouse aorta. M1 macrophages-derived EVs elevated miR-185-3p to promote development of AS pathology and levels of blood lipid, endothelial cellular adhesion, oxidative stress factors and inflammatory factors, suppressed cell proliferation and promoted cell apoptosis of vascular endothelial cells in atherosclerotic mice through downregulating Smad7. Smad7 was a target gene of miR-185-3p and miR-185-3p could inhibit expression of Smad7. CONCLUSION: M1 macrophages-derived EVs and upregulated miR-185-3p aggravated the development of AS in ApoE-/- mice by negatively regulating Smad7. This research may further the understanding of AS mechanism.

Treatment of acute pulmonary embolism using rheolytic thrombectomy.

BACKGROUND: The AngioJet rheolytic thrombectomy (ART) system can quickly fragment and aspirate thrombi according to Bernoulli's principle. AIMS: This retrospective study aimed to evaluate the therapeutic effects of the ART system in treating severe acute pulmonary embolism (APE), including high-risk pulmonary embolism (HR-PE) and intermediate-high-risk pulmonary embolism (IHR-PE). METHODS: Forty-four APE patients (21 HR-PE and 23 IHR-PE) were enrolled and underwent pulmonary ART using the 6 Fr Solent Omni AngioJet device. Nineteen patients were diagnosed with APE and lower extremity deep venous thrombosis (LEDVT), and underwent thrombectomy of APE and LEDVT simultaneously using ART. All patients also received local thrombolysis with urokinase. RESULTS: The results showed that the mean length of stay in intensive care units was 2.4±1.9 days. Significant improvements in clinical, haemodynamic and angiographic parameters were observed in both groups; the improvements in shock index, PaO2, and angiographic parameters were more obvious in the IHR-PE group. Six of the 44 patients died in hospital. During the follow-up, 35 of 38 patients were functioning well and no recurrence of APE was observed. CONCLUSIONS: Pulmonary ART plus local thrombolysis of the pulmonary artery for HR-PE or IHR-PE is feasible and appears to be safe. Further studies are warranted to investigate comparative efficacy compared to existing treatments.

LncRNA Xist induces arterial smooth muscle cell apoptosis in thoracic aortic aneurysm through miR-29b-3p/Eln pathway.

BACKGROUND: Thoracic aortic aneurysm (TAA) is a serious disease usually happening in elder people and with high death rate. Accumulating studies have reported that long non-coding RNAs (lncRNAs) are implicated in the progression of various human diseases, including TAA. AIM: In our study, we intended to explore the function of elastin (Eln) and its upstream mechanism in TAA. METHODS: RT-qPCR determined gene expressions and western blot tested changes in protein levels. Ang Ⅱ treatment was implemented to induce cell apoptosis. Flow cytometry analysis, TUNEL assay and JC-1 assay were exploited to measure cell apoptosis. Meanwhile, mechanistic assays such as RIP, RNA pull down and luciferase reporter assays were employed to identify the interplay between RNAs. RESULTS: Eln inhibition was identified to protect rat arterial smooth muscle cells from apoptosis. Also, miR-29b-3p was identified to bind to Eln, and X inactive specific transcript (Xist) could boost Eln expression through absorbing miR-29b-3p. Meanwhile, Eln overexpression counteracted the suppression of silenced Xist on the apoptosis of rat arterial smooth muscle cells. More importantly, such ceRNA network was proved to aggravate the apoptosis of human aortic smooth muscle cells. CONCLUSION: LncRNA Xist contributes to arterial smooth muscle cell apoptosis through miR-29b-3p/Eln pathway, providing new potential roads for treating TAA.

Clinical Features of COVID-19 Patients With Venous Thromboembolism.

This study aimed to assess the clinical features of coronavirus disease 2019 (COVID-19) patients with VTE, to help develop preventive measures for venous thromboembolism (VTE in COVID-19) cases. COVID-19 patients admitted to Henan Provincial People's Hospital were retrospectively analyzed, including 23, 4 and 8 cases with mild to moderate, severe and critical symptoms, respectively. VTE incidence, age at onset, relevant laboratory parameters and prognosis were analyzed. Overall, VTE incidence in the 35 patients was 20.0%, occurring in severe (n = 1) and critical (n = 6) cases. D-dimer showed statistical significance in laboratory examination, representing except a diagnostic index and especial can be a prognostic factor in VTE among COVID-19 patients. Severe and critical COVID-19 cases had significantly reduced platelet counts, with a risk of hemorrhage. During treatment, the risk of both hemorrhage and thrombosis should be considered. VTE occurs in COVID-19 cases, affecting individuals with severe and critical symptoms. Significant D-dimer increase is of great significance in the risk assessment of death in critical cases of COVID-19. Appropriate measures should be taken to prevent VTE during treatment.